This research program proposes to study the biochemical and neurochemical basis of alcohol drinking behavior in genetically selected lines of rats which exhibit natural alcohol preference (P) and aversion (nonpreference, NP) and to develop the P-line as an animal model for alcoholism. The following correlates of alcohol preference and nonpreference will be sought by comparison of the P and NP strains: 1) Innate differences in brain alcohol and acetaldehyde metabolism, alcohol and aldehyde dehydrogenase activity, (Na-K ions)-ATPase activity and the metabolism of serotonin, norepinephrine and dopamine. Acetylcholine, taurine, gamma-aminobutyric acid and other putative amino acid neurotransmitters will also be measured. 2) Differences in the acute and chronic effects of ethanol administration on brain (Na-K ions)-ATPase, calcium and the content and metabolism of neurotransmitter compounds. 3) Innate behavioral differences between the P and NP lines and differences in the effects of ethanol between the 2 lines. Whether the P-animals drink because of the orosensory or the pharmacologic effect of ethanol will be determined. The natural alcohol preference behavior of the P-strains will be maximized by techniques such as the use of sweeteners, food-restriction and operant-conditioning techniques in order to attain states of prolonged intoxication, dependence and withdrawal.